Application of Synthetic Polymeric Scaffolds in Breast Cancer 3D Tissue Cultures and Animal Tumor Models.

Girdhari Rijal,Weimin Li,Chandra Bathula

doi:10.1155/2017/8074890

Girdhari Rijal, Weimin Li + Show 1 more

Open Access

https://doi.org/10.1155/2017/8074890

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Abstract

Preparation of three-dimensional (3D) porous scaffolds from synthetic polymers is a challenge to most laboratories conducting biomedical research. Here, we present a handy and cost-effective method to fabricate polymeric hydrogel and porous scaffolds using poly(lactic-co-glycolic) acid (PLGA) or polycaprolactone (PCL). Breast cancer cells grown on 3D polymeric scaffolds exhibited distinct survival, morphology, and proliferation compared to those on 2D polymeric surfaces. Mammary epithelial cells cultured on PLGA- or PCL-coated slides expressed extracellular matrix (ECM) proteins and their receptors. Estrogen receptor- (ER-) positive T47D breast cancer cells are less sensitive to 4-hydroxytamoxifen (4-HT) treatment when cultured on the 3D porous scaffolds than in 2D cultures. Finally, cancer cell-laden polymeric scaffolds support consistent tumor formation in animals and biomarker expression as seen in human native tumors. Our data suggest that the porous synthetic polymer scaffolds satisfy the basic requirements for 3D tissue cultures both in vitro and in vivo. The scaffolding technology has appealing potentials to be applied in anticancer drug screening for a better control of the progression of human cancers.

Highlights

With the integration of the spatial concept, various 3D cell culture systems have been developed to overcome the limitations of 2D cultures
Cells grown in 3D cultures display changes in metabolic characteristics, such as increased glycolysis [8], in gene expression patterns, such as upregulation of VEGF and angiopoietin genes involved in angiogenesis [9,10,11], and in production of chemokines, such as interleukin-8 [12], compared to cells grown on 2D surfaces
To examine the survival of cancer cells grown on the polymeric substrata, human triple (ER, PR, and HER2 receptor) negative breast cancer MDA-MB-231 cells were cultured on poly(lactic-co-glycolic) acid (PLGA)-coated microscopic glass slides (2D) and porous PLGA scaffolds (3D), respectively, as described in the methods and illustrated in Figure 1(a) for 14 days

Summary

Introduction

With the integration of the spatial concept, various 3D cell culture systems have been developed to overcome the limitations of 2D cultures. Cells grown in 3D cultures display changes in metabolic characteristics, such as increased glycolysis [8], in gene expression patterns, such as upregulation of VEGF and angiopoietin genes involved in angiogenesis [9,10,11], and in production of chemokines, such as interleukin-8 [12], compared to cells grown on 2D surfaces. It is noteworthy that genome wide gene expression analysis comparing gene expression patterns of U87 cells grown in 2D and 3D cultures with a cohort of 53 pediatric high grade gliomas revealed significant similarities between the 3D, but not the 2D, culture samples and the human brain tumors [13]. Several studies have shown increased chemoresistance of cancer cells grown in 3D systems compared to the cells in 2D cultures [14,15,16], recapitulating the responses of cancer cells to chemotherapeutics in vivo. The advantages of synthetic polymeric scaffolds are their abundant availability, low cost, suitability for large-scale

Methods

Results

Conclusion